This invention relates to agrochemically useful xcex1-unsaturated amines having insecticidal/miticidal activity, their production and use.
Among xcex1-unsaturated amines, such compounds as (i) cimetidine (described for example in Journal of Medicinal Chemistry 24, 913, 1981), (ii) ranitidine (described for example in Agents Actions 11, 160, 1981) and (iii) famotidine (described for example in Journal of Medicinal Chemistry 27, 849, 1984) are known as histamine H2 receptor antagonists. 
As agricultural insecticide/miticides, organophosphorus or carbamate pesticides which are highly toxic to warm-blooded animals have heretofore been employed. However, there has been an emergence of noxious insects, particularly of the order xe2x80x9cHemipteraxe2x80x9d, which are resistant to these pesticides, and there has been a long-standing need for the development of a pesticide effective against these resistant pests.
Getting impetus from the aforementioned histamine H2 receptor antagonists, the present inventors synthesized various xcex1-unsaturated amines and investigated their activities. As a result, we discovered surprisingly that compounds of the invention which have no alkylene group or only a short alkylene group in the side chain have agriculturally useful insecticidal/miticidal activity.
Based on the above finding, the present inventors conducted further research and have come up with the present invention.
The invention is, thus, concerned with:
(1) novel xcex1-unsaturated amines of the formula: 
xe2x80x83wherein X1 and X2 are such that one is an electron-attracting group with the other being a hydrogen atom or an electron-attracting group; R1 is a group attached through a nitrogen atom; R2 is a hydrogen atom or a group attached through a carbon, nitrogen or oxygen atom; n is an integer equal to 0, 1 or 2; Axc2x0 is a heterocyclic group, with the proviso that when R2 is a hydrogen atom, R1 is a group of the formula: 
xe2x80x83wherein R3ais a hydrogen atom, C1-4 alkyl, C7-9 aralkyl or C1-4 acyl and R4ais a hydrogen atom, C1-4 alkyl, C1-4 alkoxy-C1-4 alkyl, (di-C1-4 alkylamino)-C1-4 alkyl, tri-C1-4 alkylsilyl-C1-4 alkyl, C2-4 alkenyl, or pyridyl- or thiazolyl-C1-2alkyl wherein the pyridyl or thiazolyl moiety may optionally be substituted with a halogen atom, or R3a and R4a taken together with the adjacent nitrogen atom constitute pyrrolidino and Axc2x0 is pyridyl, pyrazinyl or thiazolyl which may optionally be substituted with a halogen C1-4 alkyl, C1-4 alkylthio or C1-4 alkoxy, or a salt thereof, and
(2) insecticidal/pesticidal compositions containing an xcex1unsaturated amine of the formula: 
xe2x80x83wherein X1 and X2 are such that one is an electron-attracting group with the other being a hydrogen atom or an electron-attracting group; R1 is a group attached through a nitrogen atom; R2 is a hydrogen atom or a group attached through a carbon, nitrogen or oxygen atom; n is an integer equal to 0, 1 or 2; A is a heterocyclic group or a cyclic hydrocarbon group, with the proviso that when R1 is xcex2-N-pyrrolidinoethylamino and R2 is a hydrogen atom, A is a group of the formula: 
xe2x80x83wherein Hal is a halogen atom (e.g. Cl, Br, F, etc.), or a salt thereof, and their production.
Referring to the above formulas [Ixc2x0] and [I], one of X1 and X2 is an electron-attracting group with the other being a hydrogen atom or an electron-attracting group. The electron-attracting group represented by X1 and X2 includes, among others, cyano, nitro, C1-4alkoxy-carbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, etc.), hydroxycarbonyl, C6-10aryloxy-carbonyl (e.g. phenoxycarbonyl etc.), heterocycleoxycarbonyl wherein the heterocycle moiety is as mentioned below (e.g. pyridyloxycarbonyl, thienyloxycarbonyl, etc.), C1-4alkylsulfonyl which may be substituted with halogen (e.g. methylsulfonyl, trifluoromethylsulfonyl, ethylsulfonyl, etc.), aminosulfonyl, di-C1-4alkoxyphosphoryl (e.g. diethoxyphosphoryl, etc.), C1-4acyl which may be substituted with halogen (e.g. a C1-4alkylcarbonyl such as acetyl, trichloroacetyl, trifluoroacetyl, etc.), C1-4alkylsulfonylthiocarbamoyl (e.g. methylsulfonylthiocarbamoyl, etc.), carbamoyl and so on. One of X1 and X2 may be a halogen atom such as fluorine, chlorine, bromine or iodine, and X1 and X2 may join together with the adjacent carbon atom to form a ring such as, for example, 
Preferred examples of the group 
are O2NCHxe2x95x90.
Referring to the above formulas [Ixc2x0] and [I], R1 may be a group attached through a carbon, oxygen or sulfur atom, but a group attached through a nitrogen atom is preferred. Thus, for example, a group of the formula 
can be used. In the above formula, R3 is for example a hydrogen atom, an alkyl group (for example, a C1-6 alkyl groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, n-hexyl, etc.), an C6-10aryl group (for example, phenyl, etc.), an C7-9 aralkyl group (for example a phenylalkyl such as benzyl, etc.), a heterocyclic group as mentioned below (for example, pyridyl, etc.), a C1-4acyl group (for example, formyl, acetyl, propionyl, etc.), a C6-10 arylcarbonyl (for example, benzoyl, etc.), an alkoxycarbonyl group (for example, C1-4 alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, etc.), a C6-10 aryloxy-carbonyl group (for example, phenoxycarbonyl, etc.), a heterocycleoxycarbonyl group wherein the heterocycle moiety is as mentioned below (for example, furyloxycarbonyl, etc.), a C6-10 arylsulfonyl group (for example, phenylsulfonyl, etc.), an alkylsulfonyl group (for example, C1-4 alkylsulfonyl groups such as methylsulfonyl, etc.), a dialkoxyphosphoryl group (for example, di-C1-4 alkoxyphosphoryl groups such as diethoxyphosphoryl, etc.), an alkoxy group (for example, C1-4 alkoxy groups such as methoxy, ethoxy, etc.), a hydroxy group, an amino group, a dlalkylamino group (for example, di-C1-4 alkylamino group such as dimethylamino, diethylamino, etc.), an acylamino group (for example, C1-4 acylamino groups such as formylamino, acetylamino, propionylamino, etc.), an alkoxycarbonylamino groups (for example, C1-4 alkoxy-carbonylamino groups such as methoxycarbonylamino, etc.), an alkylsulfonylamino group (for example, C1-4 alkylsulfonylamino groups such as methylsulfonylamino, etc.), a di-alkoxyphosphorylamino group (for example, di-C1-4 alkoxyphosphorylamino groups such as diethoxyphosphorylamino, etc.), an C7-9 aralkyloxy group (for example, benzyloxy, etc.), an alkoxycarbonylalkyl group (for example, C1-4 alkoxy-carbonyl-C1-4 alkyl groups such as methoxycarbonylmethyl, etc.) or the like. R4 is for example a hydrogen atom, or an alkyl (for example, C1-4 alkyl groups such as methyl, ethyl, etc.), cycloalkyl (for example, C3-6 cycloalkyl groups such as cyclohexyl, etc.), alkenyl (for example, C2-4 alkenyl groups such as vinyl, allyl, etc.), cycloalkenyl (e.g. C3-6 cycloalkenyl groups such as cyclohexenyl, etc.) or alkynyl (for example, C2-4 alkynyl groups such as ethynyl, etc.) group which may optionally be substituted by 1 to 3 substituents (e.g. hydroxyl, C1-4 alkoxy such as methoxy, halogen such as fluorine, di-C1-4 alkylamino such as dimethylamino, C1-4 alkylthio such as i-propylthio and n-propylthio, C1-3 acylamino such as acetylamino, C1-4 alkylsulfonylamino such as methylsulfonylamino, tri-C1-4 alkylsilyl such as trimethylsilyl, pyridyl or thiazolyl which may optionally be substituted with a halogen atom, etc.). Furthermore, R3 and R4 may, taken together with the adjacent nitrogen atom, constitute a 5- or 6-membered cyclic amino group such as 
and so on.
The group attached through a nitrogen atom, represented by R1, includes an amino group which may optionally be substituted (for example by any of the alkyl, aryl, aralkyl, heterocyclic, acyl, alkoxycarbonyl, aryloxycarbonyl, heterocycleoxycarbonyl, arylsulfonyl, alkylsulfonyl, dialkoxyphosphoryl, cycloalkyl, alkenyl, cycloalkenyl and alkynyl groups mentioned in the above definition of R3 and R4) such as di-substituted amino groups, e.g. di-C1-6 alkylamino, Nxe2x80x94C1-6 alkyl-N-formylamino, etc., mono-substituted amino groups, e.g. mono-C1-6 alkylamino etc., and unsubstituted amino, a hydrazino group which may optionally be substituted (for example by any of the alkyl, acyl, alkoxycarbonyl, alkylsulfohyl, dialkoxyphosphoryl and other groups mentioned in the above definition of R3) or a hydroxyamino group which may optionally be substituted (for example by any of the alkyl, aralkyl and other groups mentioned in the above description of R3).
R2 is a hydrogen atom or a group attached through a carbon, nitrogen or oxygen atom. The group attached through a carbon atom, R2, includes, among others, C1-4 acyl (for example, formyl, acetyl, propionyl, etc.), alkyl (for example, C1-4 alkyl groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, etc.), alkenyl (for example, C2-4 alkenyl groups such as vinyl, allyl, etc.), cycloalkyl (for example, C3-6 cycloalkyl groups such as cyclopentyl, cyclohexyl, etc.), C6-10 aryl (for example, phenyl, naphthyl, etc.), C7-9 aralkyl (for example phenylalkyl such as benzyl, etc.) and heterocyclic as mentioned below which has a free bond on a carbon atom thereof (for example, 3- or 4-pyridyl, etc.). These groups may each be substituted by 1 to 3 substituents (for example, C1-4 alkylthio groups such as methylthio, ethylthio, etc., C1-4 alkoxy groups such as methoxy, ethoxy, etc., mono- or di-C1-4 alkylamino groups such as methylamino, dimethylamino, etc., C1-4 alkoxy-carbonyl groups such as methoxycarbonyl, ethoxycarbonyl, etc., C1-4 alkylsulfonyl groups such as methylsulfonyl, ethylsulfonyl, etc., halogen atoms such as fluorine, chlorine, bromine, iodine, etc., C1-4 acyl groups including alkanoyls such as acetyl, etc., benzoyl, phenylsulfonyl, pyridyl and so on). The group attached through a nitrogen atom, R2, includes, among others, the groups mentioned in the definition of R1. The group attached through an oxygen atom, R2, includes, among others, alkoxy (for example, C1-4 alkoxy groups such as methoxy, ethoxy, etc.), cycloalkoxy (for example, C3-6 cycloalkoxy groups such as cyclohexyloxy etc.), alkenyloxy (for example, C2-4 alkenyloxy groups such as vinyloxy, allyloxy, etc.), cycloalkenyloxy (for example, C3-6 cycloalkenyloxy groups such as cyclohexenyloxy etc.), alkynyloxy (for example, ethynyloxy etc.), C6-10 aryloxy (for example, phenoxy, etc.), heterocycleoxy wherein the heterocycle moiety is as mentioned below (for example, thienyloxy etc.) and hydroxyl. These groups may each have 1 to 3 substituents (for example, halogen such as fluorine, chlorine, bromine, phenyl and so on). R2 is preferably a group attached through a carbon, nitrogen or oxygen group, such as formyl, an alkyl group (particularly C1-4 alkyl groups such as methyl, ethyl, etc.) which may optionally be substituted (for example by the C1-4 alkylthio, C1-4 alkoxy, mono- or di-C1-4 alkylamino, C1-4 alkoxycarbonyl, C1-4 alkylsulfonyl, acetyl, benzoyl, phenylsulfonyl, pyridyl, etc.), an amino group which may optionally be substituted (for example, those mentioned in the definition of R1) and a hydroxyl group which may optionally be substituted for example by-the above-mentioned C1-4 alkyl, C3-6 cycloalkyl, C2-4 alkenyl, C3-6 cycloalkenyl, C2-4 alkynyl, C6-10 aryl and heterocyclic groups (particularly C1-4 alkoxy groups such as methoxy and so on). The symbol n means 0, 1 or 2. Therefore, xe2x80x94CnH2nxe2x80x94 in the formulas [Ixc2x0] and [I] represents a single bond, xe2x80x94CH2xe2x80x94, xe2x80x94CH2CH2xe2x80x94, or 
although the single bond or xe2x80x94CH2xe2x80x94 is preferred. The symbols Axc2x0 and A mean a heterocyclic group as mentioned below (such as 3-pyridyl, 6-chloro-3-pyridyl, 6-methoxy-3-pyridyl, 6-methyl-3-pyridyl, 3-quinolyl, etc.), preferably one which may optionally be substituted with one to three of the choices (i), (iv), (Viii), (XVii), (XLVi), (XLViii) and so on as mentioned below, or a cyclic hydrocarbon group as mentioned below (such as cyclopropyl, cyclohexyl, phenyl, p-chlorophenyl and so on), preferably one which may optionally be substituted with one or two of the choice (XVii) as mentioned below. The heterocyclic group of Axc2x0 or A is more preferably a pyridyl or thiazolyl group which may optionally be substituted, such as 3-pyridyl, 6-chloro-3-pyridyl, 6-bromo-3-pyridyl, 2-chloro-5-thiazolyl and so on. The cyclic hydrocarbon group A is more preferably a halophenyl group such as p-chlorophenyl and so on.
As the alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, aralkyl, heterocyclic and cyclic hydrocarbon groups in the definitions of X1, X2, R1, R2, R3, R4, Axc2x0 and A, the following groups, among others, may be employed and each of these groups may have 1 to 5 substituents such as (i) through (Lii) which appear hereinafter.
The alkyl group preferably contains 1 to 20 carbon atoms and is more preferably a group of 1 to 8 carbon atoms. This alkyl group may be straight-chain or branched. Specific examples of the alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, 2-ethylhexyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, octadecyl, nonadecyl, eicosyl and so on.
The cycloalkyl group is preferably a group of 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and so on.
The alkenyl group is preferably a group of 2 to 6 carbon atoms. Specific examples of such alkenyl group include vinyl, allyl, isopropenyl, methallyl, 1,1-dimethylallyl, 2-butenyl, 3-butenyl, 2-pentenyl, 4-pentenyl, 5-hexenyl and so on.
The cycloalkenyl group is preferably a group of 3 to 6 carbon atoms, such as 1-cyclopropenyl, 2-cyclopropenyl, 1-cyclobutenyl, 2-cyclobutenyl, 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, 1,3-cyclohexadien-1-yl, 1,4-cyclohexadien-1-yl, 1,3-cyclopentadien-1-yl, 2,4-cyclopentadien-1-yl and so on.
The alkynyl group is preferably a group of 2 to 6 carbon atoms, such as ethynyl, propargyl, 2-butyn-1-yl, 3-butyn-1-yl, 3-butyn-2-yl, 1-pentyn-3-yl, 3-pentyn-1-yl, 4-pentyn-2-yl, 3-hexyn-1-yl and so on.
The aryl group may for example be phenyl or naphthyl.
The aralkyl group may for example be benzyl, phenethyl, naphthylmethyl or the like.
The heterocyclic group includes, among others, 5- to 8-membered rings each containing 1 to 5 hetero atoms such as oxygen, sulfur and nitrogen or fused rings derived therefrom, such as 2- or 3-thienyl, 2- or 3-furyl, 2- or 3-pyrrolyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-isoxazolyl, 3-, 4- or 5-isothiazolyl, 3- or 5-(1,2,4-oxadiazolyl), 1,3,4-oxadiazolyl, 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5-(1,2,3-thiadiazolyl), 1,2,5-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1H- or 2H tetrazolyl, N-oxido-2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, N-oxido-3- or 4-pyridazinyl, benzofuryl, benzothiazolyl, benzoxazolyl, triazinyl, oxotriazinyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, morpholinyl, 1,4-thiazinyl, 1,3-thiazinyl, piperazinyl, benzimidazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthyridinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenanthridinyl, phenazinyl, phenothiazinyl, phenoxazinyl and so on.
The cyclic hydrocarbon group includes, among others, C3-6 cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc., C3-6 cycloalkenyl groups such as 1-cyclopropenyl, 2-cyclobutenyl, 1-cyclohexenyl, 2-cyclohexenyl, 1,3-cyclohexadien-1-yl, etc., and C6-10 aryl groups such as phenyl, naphthyl and so on.
(i) C1-4 Alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, etc. are used.
(ii) C3-6 Cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. are used.
(iii) C6-10 Aryl groups such as phenyl, naphthyl, etc. are used.
(iv) C1-4 Alkoxy groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, etc. are used.
(v) C3-6 Cycloalkyloxy groups such as cyclopropyloxy, cyclopentyloxy, cyclohexyloxy, etc. are used.
(vi) C6-10 Aryloxy groups such as phenoxy, naphthyloxy, etc. are used.
(vii) C7-12 Aralkyloxy groups such as benzyloxy, 2-phenethyloxy, 1-phenethyloxy, etc. are used.
(viii) C1-4 Alkylthio groups such as methylthio, ethylthio, propylthio, butylthio, etc. are used.
(ix) C3-6 Cycloalkylthio groups such as cyclopropylthio, cyclopentylthio, cyclohexylthio, etc. are used.
(x) C6-10 Arylthio groups such as phenylthio, naphthylthio, etc. are used.
(xi) C7-12 Aralkylthio groups such as benzylthio, 2-phenethylthio, 1-phenethylthio, etc. are used.
(xii) Mono-C1-4 alkylamino groups such as methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, tert-butylamino, etc. are used.
(xiii) Di-C1-4 alkylamino groups such as dimethylamino, diethylamino, dipropylamino, dibutylamino, N-methyl-N-ethylamino, N-methyl-N-propylamino, N-methyl-N-butylamino, etc. are used.
(xiv) C3-6 Cycloalkylamino groups such as cyclopropylamino, cyclopentylamino, cyclohexylamino, etc. are used.
(xv) C6-10 Arylamino groups such as anilino etc. are used.
(xvi) C7-12 Aralkylamino groups such as benzylamino, 2-phenethylamino, 1-phenethylamino, etc. are used.
(xvii) Halogen atoms such as fluorine, chlorine, bromine and iodine are used.
(xviii) C1-4 Alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarboyl, butoxycarbonyl, tert-butoxycarbonyl, isobutoxycarbonyl, etc. are used.
(xix) C6-10 Aryloxycarbonyl groups such as phenoxycarbonyl etc. are used.
(xx) C3-6 Cycloalkyloxycarbonyl groups such as cyclopropyloxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl, etc. are used.
(xxi) C7-12 Aralkyloxycarbonyl groups such as benzyloxycarbonyl, 1-phenethyloxycarbonyl, 2-phenethyloxycarbonyl, etc. are used.
(xxii) C1-5 Alkanoyl groups such as formyl, acetyl, propionyl, butyryl, pivaloyl, etc. are used.
(xxiii) C1-5 Alkanoyloxy groups such as formyloxy, acetoxy, butyryloxy, pivaloyloxy, pentanoyloxy, hexanoyloxy, heptanoyloxy, octanoyloxy, nonanoyloxy, decanoyloxy, undecanoyloxy, dodecanoyloxy, tridecanoyloxy, tetradecanoyloxy, pentadecanoyloxy, etc. are used.
(xxiv) Carbamoyl groups which may optionally be substituted, such as carbamoyl, N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl, N,N-diethylcarbamoyl, N-phenylcarbamoyl, pyrrolidinocarbamoyl, piperidinocarbamoyl, piperazinocarbamoyl, morpholinocarbamoyl, N-benzylcarbamoyl, etc. are used.
(xxv) Substituted carbamoyloxy groups such as N-methylcarbamoyloxy, N,N-dimethylcarbamoyloxy, N-ethylcarbamoyloxy, N-benzylcarbamoyloxy, N,N-dibenzylcarbamoyloxy, N-phenylcarbamoyloxy, etc. are used.
(xxvi) C1-4 Alkanoylamino groups such as formylamino, acetamido, propionamide, butyramido, etc. are used.
(xxvii) C6-10 Arylcarbonylamino groups such as benzamido etc. are used.
(xxviii) C1-4 Alkoxycarbonylamino groups such as methoxycarbonylamino, ethoxycarbonylamino, butoxycarbonylamino, tert-butoxycarbonylamino, etc. are used.
(xxix) C7-12 Aralkyloxycarbonylamino groups such as benzyloxycarbonylamino, 4-methoxybenzyloxycarbonylamino, 4-nitrobenzyloxycarbonylamino, 4-chlorobenzyloxycarbonylamino, etc. are used.
(xxx) Substituted sulfonylamino groups such as methanesulfonylamino, ethanesulfonylamino, butanesulfonylamino, benzensulfonylamino, toluenesulfonylamino, naphthalenesulfonylamino, trifluoromethanesulfonylamino, 2-chloroethanesulfonylamino, 2,2,2-trifluoromethanesulfonylamino, etc. are used.
(xxxi) Heterocyclic groups nuclearly containing 1 to 5 hetero atoms of N, O and/or S, such as pyrrolidinyl, pyrrolyl, pyrazolyl, imidazolyl, furyl, thienyl, oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, piperidinyl, pyridyl, piperazinyl, pyrimidinyl, pyranyl, tetrahydropyranyl, tetrahydrofuryl, indolyl, quinolyl, 1,3,4-oxadiazolyl, thieno[2,3-d]pyridyl, 1,2,3-thiadiazolyl, 1,3,4-thladiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl, tetrazolyl, 4,5-dihydro-1,3-dioxazolyl, tetrazolo[1,5-b]pyridazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, etc. are used.
(xxxii) Heterocyclethio, heterocycleoxy, heterocycleamino, and heterocyclecarbonylamino groups and groups derived therefrom by attachment of any of heterocyclic groups (xxxi) to the S, O, N atom or the carbonylamino group are used.
(xxxiii) Di-C1-4 alkylphosphinothioylamino groups such as dimethylphosphinothioylamino, diethylphosphinothioylamino, etc. are used.
(xxxiv) Alkoxyimino groups such as methoxyimino, ethoxyimino, 2-fluoroethoxyimino, carboxymethoxyimino, 1-carboxy-1-methylethoxyimino, 2,2,2-trichloroethoxycarbonylmethoxyimino, 1-(2,2,2-trichloroethoxycarbonyl)-1-methylethoxyimino, (2-aminothiazol-4-yl)methoxyimino, (1H-imidazol-4-yl)methoxyimino, etc. are used.
(xxxv) C1-4 Alkylsulfonyloxy groups such as methanesulfonyloxy, ethanesulfonyloxy, butanesulfonyloxy, etc. are used.
(xxxvi) C6-10 Arylsulfonyloxy groups such as benzenesulfonyloxy, toluenesulfonyloxy, etc. are used.
(xxxvii) Di-C6-10 arylphosphinothioylamino groups such as diphenylphosphinothioylamino, etc. are used.
(xxxviii) Thiocarbamoylthio groups which may optionally be substituted, such as thiocarbamoylthio, N-methylthiocarbamoylthio, N,N-dimethylthiocarbamoylthio, N-ethylthiocarbamoylthio, N-benzylthiocarbamoylthio, N,N-dibenzylthiocarbamoylthio, N-phenylthiocarbamoylthio, etc. are used.
(xxxix) Silyloxy groups such as trimethylsilyloxy, t-butyldimethylsilyloxy, t-butyldiphenylsilyloxy, dimethylphenylsilyloxy, etc. are used.
(xL) Silyl groups such as trimethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, dimethylphenylsilyl, etc. are used.
(xLi) C1-4 Alkylsulfinyl groups such as methylsulfinyl, ethylsulfinyl, propylsulfinyl, butylsulfinyl, etc. are used.
(xLii) C6-10 Arylsulfinyl groups such as phenylsulfinyl, naphthylsulfinyl, etc. are used.
(xLiii) C1-4 Alkylsulfonyl groups such as methanesulfonyl, ethanesulfonyl, butanesulfonyl, etc. are used.
(xLiv) C6-10 Arylsulfonyl groups such as benzenesulfonyl, toluenesulfonyl, etc. are used.
(xLv) C1-4 Alkoxycarbonyloxy groups such as methoxycarbonyloxy, ethoxycarbonyloxy, tert-butoxycarbonyloxy, etc. are used.
(xLvi) Halo-C1-4 alkyl groups such as trifluoromethyl, 1,1,2,2-tetrafluoroethyl, difluoromethyl, monofluoromethyl, trichloromethyl, dichloromethyl, monochloromethyl, etc. are used.
(xLvii) Halo-C1-4 alkoxy, halo-C1-4 alkylthio, halo-C1-4 alkylsulfinyl and halo-C1-4 alkylsulfonyl groups as well as groups derived therefrom by attachement of any of halo-C1-4 alkyl groups (xLvi) to the O, S, sulfinyl and sulfonyl moieties thereof are used.
(xLviii) Cyano, nitro, hydroxy, carboxyl, sulfo and phosphono groups are used.
(xLix) C1-4 Alkyloxysulfonyl groups such as methoxysulfonyl, ethoxysulfonyl, butoxysulfonyl, etc. are used.
(L) C6-10 Aryloxysulfonyl groups such as phenoxysulfonyl, tolyloxysulfonyl, etc. are used.
(Li) C7-12 Aralkyloxysulfonyl groups such as benzyloxysulfonyl, 2-phenethyloxysulfonyl, 1-phenethyloxysulfonyl, etc. are used.
(Lii) Di-C1-4-alkyloxyphosphoryl groups such as dimethoxyphosphoryl, diethoxyphosphoryl, dibutoxyphosphoryl, etc. are used.
Preferred examples of the unsaturated amines of formulas [Ixc2x0] and [I] or salts thereof include:
The xcex1-unsaturated amines of the formula: 
wherein R1a is a mono-C1-6 alkylamino group, an Nxe2x80x94C1-6 alkyl-N-formylamino group or an amino group; R2a is an C1-4 alkyl group or an C1-4 alkoxy group; Aa is a chloropyridyl group, or salts thereof;
the xcex1-unsaturated amines of the formula: 
xe2x80x83wherein R1b is a mono-C1-6 alkylamino group or an Nxe2x80x94C1-6 alkyl-N-formylamino group; Aa has the meaning defined hereinbefore, or salts thereof;
the xcex1-unsaturated amines of the formula: 
xe2x80x83wherein R1c is a di-C1-6 alkylamino group; R2b is a hydrogen atom, a formyl group or an C1-4 alkyl group; Ab is a pyridyl group or a chloropyridyl group, or salts thereof; and
the xcex1-unsaturated amines of the formula: 
xe2x80x83wherein the symbols have the meanings defined hereinbefore, or salts thereof.
Referring to the above formulas [Ia], [Ib] and [Ic], the mono-C1-6 alkylamino group represented by R1a or R1b includes, among others, monomethylamino, monoethylamino, mono-n-propylamino, mono-i-propylamino, mono-n-butylamino, mono-i-butylamino, mono-n-hexylamino, etc. and preferably mono-C1-4-alkyl amino groups such as mono-methylamino, monoethylamino and so on. The Nxe2x80x94C1-6 alkyl-N-formylamino group represented by R1a or R1b includes, among others, N-methyl-N-formylamino, N-ethyl-N-formylamino, N-n-propyl-N-formylamino, N-i-propyl-N-formylamino, N-n-butyl-N-formylamino, N-n-hexyl-N-formylamino, etc. and preferably Nxe2x80x94C1-4 alkyl-N-formylamino groups such as N-methyl-N-formylamino, N-ethyl-N-formylamino and so on. The di-C1-6 alkylamino group represented by R1c includes, among others, dimethylamino, N-ethyl-N-ethylamino, diethylamino, di-n-propylamino, di-i-propylmino, di-n-butylamino, di-i-butylamino, di-n-pentylamino, di-i-pentylamino, di-n-hexylamino, etc. and preferably di-C1-4 alkylamino groups such as dimethylamino, N-ethyl-N-methylamino and diethylamino. The C1-4 alkyl group represented by R2a or R2c includes, among others, the alkyl groups mentioned in the definition of R2 above and preferably methyl, ethyl and so on. The C1-4 alkoxy group represented by R2a includes, among others, the alkoxy groups mentioned in the definition of R2 above and preferably methoxy, ethoxy and so on. the chloropyridyl group represented by Aa or Ab includes, among others, 2-chloro-3-pyridyl, 4-chloro-3-pyridyl, 5-chloro-3-pyridyl, 6-chloro-3-pyridyl, 3-chloro-4-pyridyl, etc. and preferably 6-chloro-3-pyridyl and so on. The pyridyl group represented by Ab includes 3-pyridyl, 4-pyridyl, etc. and preferably 3-pyridyl.
Typical xcex1-unsaturated amines of formulas [Ixc2x0] and [I] or salts thereof include:
The xcex1-unsaturated amines of the formula: 
wherein X2a is a hydrogen atom, C1-4 alkoxycarbonyl or C1-4 alkylsulfonylthiocarbamoyl; R2c is a hydrogen atom, C1-3 acyl, C1-4 alkyl, mono- or di-C1-4 alkoxy-C1-4 alkyl, C7-9 aralkyl, mono- or di-C1-4 alkylamino or C1-4 alkoxy; Ac is 3- or 4-pyridyl, pyrazinyl or 4- or 5-thiazolyl which may optionally be substituted with halogen, C1-4 alkyl or C1-4 alkoxy; and R3a, R4a and n are as defined above, or salts thereof;
the xcex1-unsaturated amines of the formula: 
xe2x80x83wherein X2a is a hydrogen atom, C1-4 alkoxycarbonyl or C1-4 alkylsulfonylthiocarbamoyl; R1d is amino, mono- or di-C1-4 alkylamino, Nxe2x80x94C1-4 alkyl-Nxe2x80x94C1-3 acylamino, C7-9 aralkylamino, halogenothiazolyl-C-1-2 alkylamino or C1-4 alkoxy-C1-2 alkylamino; R2c is a hydrogen atom, C1-3 acyl, C1-4 alkyl, mono- or di-C1-4 alkoxy-C1-4 alkyl, C7-9 aralkyl, mono- or di-C1-4 alkylamino or C1-4 alkoxy; n is an integer equal to 0, 1 or 2; and Ad is 3- or 4-pyridyl, pyrazinyl or 5-thiazolyl which may optionally be substituted with halogen, C1-4 alkyl or C1-4 alkoxy, or salts thereof;
the xcex1-unsaturated amines of the formula: 
xe2x80x83wherein X2b is a hydrogen atom or C1-2alkylsulfonylthiocarbamoyl; R1e is amino, mono- or di-C1-2alkylamino or Nxe2x80x94C1-2alkyl-N-formylamino; R2d is a hydrogen atom, C1-2alkyl or C1-3acyl; and Ae is a group of the formula: 
xe2x80x83wherein Hal is a halogen atom, or salts thereof;
the xcex1-unsaturated amines of the formula: 
xe2x80x83wherein X2c is a hydrogen atom or methylsulfonylthiocarbamoyl; R1f is amino, methylamino, dimethylamino or N-methyl-N-formylamino; R2d is a hydrogen atom, formyl or C1-2alkyl; and Ae is a group of the formula: 
xe2x80x83wherein Hal is a halogen atom, or salts thereof; and
the xcex1-unsaturated amines of the formula: 
xe2x80x83wherein R1e is amino, mono- or di-C1-2alkylamino or Nxe2x80x94C1-2alkyl-N-formylamino; R2e is C1-2alkyl or formyl; and Hal is a halogen atom, or salts thereof.
In the above formulas [Ie] to [Ii], the groups represented by X2a, X2b and X2c, the groups represented by R1d, R1e and R1f, the groups represented by R2c, R2d and R2e, and the groups represented by Ac, Ad and Ae are as mentioned above in the case of X2, R1, R2, Axc2x0 and A.
The compound [I] or its salt can be produced by the analogous known processes and further by the following processes, for instance. 
wherein X1, X2, R1, R2, n and A have the meanings defined hereinbefore; R5 is an C1-4 alkyl group such as methyl, ethyl, etc. or an C7-9aralkyl group such as benzyl etc.; Y is a hydrogen atom or an alkali metal such as sodium, potassium, etc. 
wherein X1, X2, R1, R2, R3, R4, R5, n and A have the meanings defined hereinbefore. 
wherein Hal is the meanings defined hereinbefore. 
wherein X1, X2, R1, R2, Hal, n and A have the meanings defined hereinbefore. 
wherein X1, X2, R1, R2, Hal, n and A have the meanings defined hereinbefore. 
wherein R1, R2, n, A and R5 have the meanings defined hereinbefore; X3 is an electron-attracting group. 
wherein X1, X2, R1, R2, n and A have the meanings defined hereinbefore; R6 is a group attached through a nitrogen atom containing at least one hydrogen atom.
In the processes 1) to 7), the compounds [III], [IV] [V], [VI], [IX], [IXxe2x80x2], [IXxe2x80x3], [X], [XIV], [XVI], [XVII], [XVIII], [XIX], [I-5], [I-6] and so on may be used in a form of a salt (e.g. one as mentioned below in a salt of the compound [I]).
In accordance with the aforementioned Process 1), a compound of general formula [II] is reacted with an amino compound of general formula [III] or a salt thereof to give a compound of general formula [IV] which is then reacted with an amino compound of general formula [V] or a salt thereof, or a compound of general formula [II] is reacted with a compound of general formula [V] to give a compound of general formula [VI] which is then reacted with a compound of general formula [III], to thereby give a compound [I]. In practicing the Process 1), the reactions of [II]xe2x86x92[IV], [IV]xe2x86x92[I], [II]xe2x86x92[VI] and [VI]xe2x86x92[I] may respectively be conducted in an appropriate solvent. There is no limitation on such a solvent provided that it does not interact with the reactant, reagent or reaction product to give byproducts but a solvent capable of dissolving both the reactant and reagent is preferred. As examples of such solvent, there may be mentioned alcohols such as methanol, ethanol, propanol, butanol, etc., aromatic hydrocarbons such as benzene, toluene, xylene, etc., ethers such as diethylether, dipropyl ether, dibutyl ether, tetrahydrofuran, dioxane, etc., nitrites such as acetonitrile, propionitrile, etc., acid amides such as dimethylformamide, dimethylacetamide, etc., sulfoxides such as dimethyl fulfoxide etc., sulfones such as sulfolane, etc., and phosphoramides such as hexamethylphosphoramide etc., as well as various mixtures thereof and mixtures thereof with water. While each of the above reactions is generally conducted at atmospheric pressure, it is possible to conduct the reaction under reduced pressure as taught by Japanese Unexamined Patent Application KOKAI-62-138478 (1987) to remove the byproduct low-boiling thiol and thereby suppress the secondary reaction. When a low-boiling solvent is used, the reaction is preferably conducted at supratmospheric pressure. For the aforesaid respective reactions, the reaction temperature may range from 30 to 150xc2x0 C. and preferably from 50 to 150xc2x0 C. The reaction time is generally 5 minutes to 48 hours, depending on the reaction temperature, reactant, reagent and solvent. The proportions of reagents [III] and [V] in the reactions [II]xe2x86x92[IV] and [II]xe2x86x92[VI] may each be 1 to 1.2 molar equivalents relative to [II]. The use of [III] and [V] in further excess is preferably avoided to prevent by-production of the diamino compound. As the reaction [II]xe2x86x92[IV] and [II]xe2x86x92[VI] in a concentrated reaction mixture may occasionally give the by-product, the diamino compound, it is desirable to avoid the reactions in such condition. The proportions of reagents [V] and [III] in the reactions [IV]xe2x86x92[I] and [VI]xe2x86x92[I] are generally 1 to 1.5 molar equivalents and, unlike in the reactions [II]xe2x86x92[IV] and [II]xe2x86x92[VI], the use of [V] or [III] in greater excess may not occasionally induce byproduct formation. A base may be permitted to be concomitantly present for the purpose of promoting the reaction or suppressing secondary reactions. As the base for such purposes, there may be used organic bases such as triethylamine, N-methylmorpholine, pyridine, 1,8-diazabicyclo[5,4,0]-7-undecene, 1,5-azabicyclo[4,3,0]non-5-ene, etc. and inorganic bases such as potassium carbonate, potassium hydrogen carbonate, sodium carbonate, sodium hydrogen carbonate, lithium carbonate, lithium hydrogen carbonate and so on. Where an alkali metal salt of reagent [III] or [V] is used, the sodium salt, lithium salt, potassium salt, etc. can be employed. The compound [IV] or [VI] may be isolated and purified by conventional procedures such as concentration, concentration under reduced pressure, pH adjustment, redistribution, solvent extraction, distillation, crystallization, recrystallization, chromatography, etc. and subjected to the next reaction. Alternatively the reaction mixture containing [IV] or [VI] may be such be directly used as the starting reactant for the next reaction.
The starting compound of general formula [II] for Process 1) can be synthesized by the procedures described in Chem. Ber. 100, 591 (1967), Acta. Chem. Scand. 22, 1107 (1968), Synthesis 1986, 967, Chem. Ber. 95, 2861 (1962), Tetraheron 30, 2413 (1974), Synthesis 1984, 797 and other literature or by procedures analogous thereto. The compound [III] can be synthesized by the procedures described in Organic Functional Group Preparations, Academic Press, Vol 1, Chapter 13 (1968) and Vol 3, Chapter 10 (1972) and other literature or by procedures analogous thereto, and the compound [V] can be synthesized by the procedures described in Survey of Organic Syntheses, Wiley-Interscience (1970), Chapter 8 and other literature or by procedures analogous thereto.
The aforementioned Process 2) comprises (1) reacting an amino compound of general formula [III] (Y=H) or an alkali metal salt (e.g. Na or K salt) with an isothiocyanic ester of general formula [VII] to give a thiourea of general formula [VIII], then reacting said thiourea [VIII] with the compound of the formula: R5I (e.g. methyl iodide, etc.) to give an isothiourea of general formula [IX], and reacting [IX] with an active methylene compound of general formula [X], (2) reacting an amino compound of general formula [III] (Y=H) or an alkali metal salt thereof with an isothiocyanic ester [VIIxe2x80x2], then reacting the resulting thiourea [VIIIxe2x80x2] with the compound of the formula: R5I (e.g. methyl iodide, etc.) to give an isothiourea [IXxe2x80x2] and reacting [IXxe2x80x2] with an active methylene compound [X], or (3) reacting an amino compound of general formula [V] (Y=H) or an alkali metal salt thereof with an isothiocyanic acid ester [VIIxe2x80x3], reacting the resulting thiourea [VIIIxe2x80x3] with the compound of the formula: R5I (e.g. methyl iodide, etc.), and reacting the resulting isothiourea [IXxe2x80x3] with an active methylene compound, to thereby give the desired compound [I].
Referring to Process 2), the reactions [III]Y=Hxe2x86x92[VIII], [III]Y=Hxe2x86x92[VIIIxe2x80x2] and [V]Y=Hxe2x86x92[VIIIxe2x80x3] and the reactions [VIII]xe2x86x92[IX], [VIIIxe2x80x2]xe2x86x92[IXxe2x80x2] and [VIIIxe2x80x3]xe2x86x92[IXxe2x80x3] can each be conducted by the known procedures described in the literature or by procedures analogous thereto. As said literature, there may be mentioned Chemical Society of Japan (ed.): Shin Jikken Kagaku Koza (New Series of Experimental Chemistry), Vo. 14, III, Maruzen (1978), Chapters 7 and 21; Organic Functional Group Preparations, Vol. 2, Academic Press (1971), Chapters 6 and 7, ditto The Second Edition (1986), and so on.
Each of the reactions [III]Y=Hxe2x86x92[VIII], [III]Y=Hxe2x86x92[VIIIxe2x80x2], and [V]Y=Hxe2x86x92[VIIIxe2x80x3] can be conducted in an appropriate solvent. There is no limitation on such a solvent provided that it does not interact with the reactant or the reagent but it is preferable to select a solvent capable of dissolving both the reactant and reagent. As examples of such solvent, there may be mentioned aromatic hydrocarbons such as benzene, toluene, xylene, etc.; aliphatic hydrocarbons such as pentane, hexane, heptane, petroleum ether, ligroine, petroleum benzene, etc.; ethers such as diethyl ether, dipropyl ether, dibutyl ether, tetrahydrofuran, dioxane, etc.; acid amides such as dimethylformamide, dimethylacetamide, etc.; sulfoxides such as dimethyl suilfoxide etc.; sulfones such as sulfolane etc.; phosphoramides such as hexanethylphosphoramide etc.; and halogenated hydrocarbons such as chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, etc. as well as various mixtures thereof. The reaction temperature is about xe2x88x9230xc2x0 to 200xc2x0 C. and preferably 0 to 150xc2x0 C. The reaction time varies with such conditions as reaction temperature, reactant, reagent, reaction system concentration and solvent, but generally in the range of 1 minute to 24 hours.
The proportions of compounds [VII], [VIIxe2x80x2] and [VIIxe2x80x3] required for the respective reactions may range from 0.5 to 2 molar equivalents, preferably 0.8 to 1.2 molar equivalents, relative to [III]Y=H, [III]Y=H and [V]Y=H. The compounds [VIII], [VIIIxe2x80x2] and [VIIIxe2x80x3] thus obtained can each be subjected to the next reaction either without isolation or after isolation from the reaction mixture by the known procedure.
Each of the reactions [VIII]xe2x86x92[IX], [VIIIxe2x80x2]xe2x86x92[IXxe2x80x2] and [VIIIxe2x80x3]xe2x86x92[IXxe2x80x3] may also be conducted in a solvent. In addition to the solvents mentioned for the reactions [III]Y=Hxe2x86x92[VIII], [III]Y=Hxe2x86x92[VIIIxe2x80x2] and [V]Y=Hxe2x86x92[VIIIxe2x80x3], such other solvents as alcohols, e.g. methanol, ethanol, propanol, butanol, etc.; ketones, e.g. acetone, methyl ethyl ketone, etc.; and esters, e.g. methyl acetate, ethyl acetate, butyl acetate, methyl formate, ethyl formate, ethyl propionate, etc. can also be employed. The reagent methyl iodide may be utilized as the solvent. For the purpose of promoting the reaction and minimizing the formation of byproducts, a base may be permitted to he present in the reaction system or permitted to act on the reaction system before or after the reaction and there are cases in which such practice contributes to improved results. As the base that can be used for the above purpose, there may be mentioned sodium hydride, sodium metal, alcoholates such as sodium ethoxide, sodium methoxide, potassium tert-butoxide, etc., organic bases such as triethylamine, diisopropylethylamine, pyridine, N,N-dimethylaniline, etc. and inorganic bases such as potassium carbonate and so on. The proportion of the base is preferably 0.8 to 1.2 molar equivalents relative to [VIII], [VIIIxe2x80x2] or [VIIIxe2x80x3]. In the absence of a base in the reaction system, [IX], [IXxe2x80x2] or [IXxe2x80x3] is formed as the hydroiodide so that this hydroiodide must be neutralized to obtain [IX], [IXxe2x80x2] or [IXxe2x80x3]. The base for this purpose is preferably a water-soluble inorganic base such as sodium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide and so on. The reaction temperature is 0 to 100xc2x0 C. and preferably 20 to 80xc2x0 C. The reaction time is generally 0.1 to 24 hours. The proportion of methyl iodide required for the reaction is not less than 1 molar equivalent relative to [VIII], [VIIIxe2x80x2] or [VIIIxe2x80x3] and may be used in a larger amount as the solvent. The [IX], [IXxe2x80x2] or [IXxe2x80x3] thus produced may be isolated by the conventional procedure before submission to the next reaction or the reaction product mixture may be directly used as the starting material in the next reaction.
Each of the reactions [IX]xe2x86x92[I-1], [IXxe2x80x2]xe2x86x92[I-2] and [IXxe2x80x3]xe2x86x92[I-3] can be conducted in accordance with the procedures described in Tetrahedron 37, 1453 (1981) Indian Journal of Chemistry 15B, 297 (1977) and other literature. The reaction may be conducted using the active methylene compound [X] in excess as a solvent or may be carried out in a different solvent. As the solvent just mentioned above, there may be used aromatic hydrocarbons such as benzene, toluene, xylene, etc., aprotic polar solvents such as dimethylformamide, dimethylacetamide, dimethyl sulfoxide, sulfolane, hexamethylphosphoramide, etc., and ethers such as tetrahydrofuran, dioxane and so on. Particularly where an aprotic polar solvent is used and the reaction is conducted under reduced pressure with the byproduct methylmercaptan being dispelled out of the reaction system, the formation of byproducts can be suppressed and the reaction yield improved. The reaction may also be conducted in the presence of a catalyst. As such catalyst, there may be employed zinc chloride, zinc bromide, zinc iodide, cupric chloride and so on. The reaction temperature is 30 to 200xc2x0 C., preferably 50-150xc2x0 C. The reaction time is generally 0.1 to 48 hours. The proportion of active methylene compound [X] necessary for the reaction is 1 to 5 molar equivalents relative to [IX], [IXxe2x80x2] or [IXxe2x80x3]. Where [X] is a low-boiling compound, it can be used in a solvent amount.
The starting compounds [VII], [VIIxe2x80x2] and [VIIxe2x80x3] can be synthesized by the procedures described in Organic Functional Group Preparations, Vol. 1, Academic Press (1968), Chapter 12 and other literature or by procedures analogous thereto, and the compound [X] can be synthesized by procedures described in Formation of Cxe2x80x94C Bonds, Vol. 1, Georg Thieme Publishers, Stuttgart (1973) and other literature.
The aforementioned Process 3) comprises reacting a compound [XI] or [XII] with an amino compound of general formula [III] or a salt thereof (e.g. the salt of an alkali metal such as Na or K) and reacting the resulting product further with an amino compound of general formula [V] or a salt (alkali metal salt) thereof or, alternatively, reacting a compound [XI] or [XII] with an amino compound of general formula [V] or a salt thereof and then reacting the resulting product with an amino compound of general formula [III] or a salt thereof to give the desired compound [I].
The reactions in Process 3) can be conducted in the same manner as those in Process 1) and the reaction conditions described for Process 1) can be utilized.
However, since compounds [XI] and [XII] are generally more reactive than compound [II], the reactions are preferably conducted under somewhat milder conditions as compared with Process 1).
The compounds [XI] and [XII] can be prepared by procedures described in Chemical Abstracts 44, 1011f, Journal of Organic Chemistry 25, 1312 (1960) and other literature or by procedures analogous thereto.
The aforementioned Process 4) comprises reacting an acid amide of general formula [XIII] or an acid amide of general formula [XV] with a halogenating agent to give a halide of general formula [XIV] or [XVI] and reacting the halide with an amino compound of general formula [V] or a salt thereof or an amino compound of general formula [III] or a salt thereof to give the desired compound [I].
The reaction of [XIII]xe2x86x92[XIV] and that of [XV]xe2x86x92[XVI] are preferably conducted in a solvent. As such solvent, there may be mentioned halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, etc., ethers such as diethyl ether, tetrahydrofuran, dioxane, etc., nitriles such as acetonitrile, propionitrile, etc. and so on. This reaction is preferably carried out under anhydrous conditions. The halogenating agent may for example be phosphorus pentachloride, hosphorus oxychloride, phosphorus trichloride, thionyl chloride, oxalyl chloride or the like. The proportion of the halogenating agent is 1 to 10 molar equivalents, preferably 1 to 5 molar equivalents, relative to [XIII] or [XV]. Preferably a base is permitted to be present in the reaction system in order to trap the byproduct hydrogen chloride, and as such base, there may be used various organic bases such as pyridine, triethylamine, diisopropylethylamine, N-methylmorpholine, N,N-dimethylaniline, N,N-diethylamine and so on. The reaction temperature is xe2x88x9280xc2x0 to 100xc2x0 C. and preferably xe2x88x9250xc2x0 to 50xc2x0 C. The reaction time is generally 0.1 to 24 hours, depending on the reactant, base, solvent, reaction Concentration and reaction temperature. The products [XIV] and [XVI] can be isolated and purified by the aforementioned known procedures before submission to the next reaction or the reaction product mixture may be directly used in the next reaction.
The reaction of [XIV]xe2x86x92[I] and that of [XVI]xe2x86x92[I] can each be conducted in a solvent similar to those mentioned for the reactions of [XIII]xe2x86x92[XIV] and [XV]xe2x86x92[XVI], preferably under anhydrous conditions. The proportion of [V] or a salt thereof and that of [III] or a salt thereof are 1 to 10 molar equivalents, preferably 1 to 5 molar equivalents, relative to [XIV] and [XVI], respectively. For the purpose of trapping the byproduct hydrogen chloride, [V] or a salt thereof or [III] or a salt thereof can be used in excess but for economy, a different base is preferably permitted to be present. A such base, there may be used any of the bases mentioned for the reactions of [XIII]xe2x86x92[XIV] and [XV]xe2x86x92[XVI]. The reaction temperature is xe2x88x9280xc2x0 C. to 100xc2x0 C. and preferably xe2x88x9250xc2x0 C. to 50xc2x0 C. The reaction time is generally 0.1 to 24 hours. The starting compounds [XIII] and [XV] can be synthesized by the procedures described in Formation of Cxe2x80x94C Bonds, Vol. 1, Georg Thieme Publishers, Stuttgart (1973) and Chemical Society of Japan(ed.): xe2x80x98Shin Jikken Kagaku Kozaxe2x80x99 (New Series of Experimental Chemistry), Vol. 14, II, Maruzen (1977), Chapters 5 and 7 and other literature or by procedures analogous thereto.
The aforementioned Process 5) comprises reacting a compound of general formula [XVII] with a halide of general formula [XVIII] to give the desired compound [I].
The reaction according to Process 5) is preferably conducted in an appropriate solvent. As such solvent, there may be employed acid amides such as dimethylformamide, dimethylacetamide, etc., sulfoxides such as dimethyl sulfoxide etc., sulfones such as sulfolane etc., phosphoramides such as hexamethylphosphoramide etc., ethers such as tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diethylene glycol dimethyl ether, etc., and so on. Mixtures of such solvents may likewise be employed. This reaction is preferably conducted in the presence of a base. As such base, there may be mentioned sodium hydride, potassium hydride, lithium hydride, calcium hydride, n-butyllithium, lithium diisopropylamide, sodium amide and so on. It is preferable that the compound [XVII] be converted to the salt of said base before it is subjected to the reaction. The proportion of the base is preferably 1 to 1.5 molar equivalents relative to [XVII]. This reaction is preferably conducted under anhydrous conditions and may be carried out in an atmosphere of nitrogen gas or argon gas. The proportion of [XVIII] is 1 to 2 molar equivalents, preferably 1 to 1.5 molar equivalents, relative to [XVII]. The reaction temperature is xe2x88x9270xc2x0 C. to 150xc2x0 C. and preferably xe2x88x9250xc2x0 C. to 100xc2x0 C. The reaction time is generally 0.1 to 48 hours.
The compound [XVII] can be easily prepared, for example by using a compound of general formula R2NH2 wherein R2 has the meaning defined hereinbefore, instead of compound [III] in said Processes 1 through 4). The compound [XVIII] can be synthesized by the process described in Organic Functional Group Preparations, Vol. 1, Academic Press (1968), Chapter 6 and other literature or by procedures analogous thereto.
The aforementioned Process 6) comprises subjecting a compound of general formula [XIX], which falls within the category of compound [I], to hydrolysis reaction and, then, to decarboxylation reaction to give a compound of general formula [I-4] which falls within the category of compound [I].
The above hydrolysis reaction can be conducted under the conditions of hydrolysis of esters which are known in the art.
Thus, in a solvent (inclusive of a solvent mixture) such as water, alcohols (e.g. methanol, ethanol, propanol, butanol, diethylene glycol, 2-methoxyethanol, etc.), ketones (e.g. acetone etc.), ethers (e.g. tetrahydrofuran, dioxane, ditnethoxyethane, etc.), amides (e.g. dimethylformamide, dimethylacetamide, hexamethylphosphoramide, etc.), sulfoxides (e.g. dimethyl sulfoxide etc.), sulfones (e.g. sulfolane etc.) and carboxylic acids (e.g. formic acid, acetic acid, etc.), the hydrolysis reaction can be conducted using an acid (for example, mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, etc., organic acids such as p-toluenesulfonic acid etc., strongly acidic ion exchange resins, and so on) or a base (for example, sodium hydroxide, potassium hydroxide, potassism carbonate, sodium hydrogen carbonate, barium hydroxide, calcium hydroxide, sodium methoxide, ammonia and so on), although the use of a base is preferred. The proportion of the base is about 1 to 10 molar equivalents, preferably about 1.2 to 4 molar equivalents, relative to [XIX]. The reaction temperature is about xe2x88x9220xc2x0 C. to 200xc2x0 C., preferably about xe2x88x925xc2x0 C. to 120xc2x0 C., and the reaction time is about 0.1 to 48 hours, preferably about 0.1 to 24 hours.
The decarboxylation reaction proceeds simultaneously with said hydrolysis reaction in many cases and usually no special procedure is required. If necessary, this reaction may be carried out by heating in the hydrolysis solvent. The reaction temperature is generally about 0 to 200xc2x0 C., preferably 30 to 150xc2x0 C., and the reaction time is 0.1 to 48 hours and preferably 0.1 to 24 hours.
The aforementioned Process 7) comprises subjecting a compound of general formula [I-5] or a compound of general formula [I-6] to alkylation, acylation, alkoxycarbonylation, sulfonylation or phosphorylation to give a compound [I].
For alkylation, the amino group in [I-5] or [I-6] is alkylated with an alkylating agent such as an alkyl chloride, alkyl bromide, alkyl iodide, dialkyl sulfate or the like. The proportion of the alkylating agent is about 1 to 3 equivalents relative to the starting compound in many instances. This alkylation reaction may be conducted under the same conditions as those described for Process 5).
The acylation, sulfonylation, phosphorylation and alkoxycarbonylation reaction can each be conducted by procedures known per se or by procedures analogous thereto.
The acylating agent for said acylation reaction may for example be an acyl halide or acid anhydride containing a group of R1 or R2. The sulfonylating agent for said sulfonylation reaction may for example be a sulfonyl halide or sulfonic anhydride containing a group of R1 or R2. The alkoxycarbonylating agent for said alkoxycarbonylation reaction may for example an alkoxycarbonyl halide or carbonate containing a group of R1 or R2. The preferred halogens in the above-mentioned halide reagents are bromine and chlorine. The proportion of each such reagent is at least one molar equivalent, preferably about 1 to 5 molar equivalents, relative to the starting compound. Where an acid anhydride is used as the acylating agent in the above acylation reaction, it can be employed in excess. These reactions are carried out in a solvent capable of dissolving the compound [I-5] or [I-6] and the respective reagents and as preferred examples of such solvent, there may be mentioned dichloromethane, chloroform, dichloroethane, tetrahydrofuran, dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, hexamethylphosphorotriamide, pyridine and so on. The reaction temperature is about xe2x88x9250xc2x0 C. to 150xc2x0 C. and the reaction time is about 0.1 to 48 hours. The reaction may be hastened and the secondary reactions suppressed to improve the yield when the reaction is conducted in the concomitant presence of an amine such as triethylamine, dimethylaminopyridine, pyridine, N,N-dimethylaniline, N,N-diethylaniline, etc., sodium hydride, potassium hydride, sodium amide, n-butyllithium, lithium diisopropylamide or the like.
The object compound [I] or salt thereof thus produced can be isolated and purified by conventional procedures such as concentration, concentration under reduced pressure, distillation, fractional distillation, pH adjustment, redistribution, solvent extraction, crystallization, recrystallization, chromatography and so on.
Where the compound [I] is obtained as the free compound, it can be converted to a agrochemically useful salt and where a salt is obtained, it can be converted to the free compound [I], using the conventional procedure in either case. Where the compound [I] contains acidic groups such as carboxyl, sulfo and/or phosphono groups in its positions X1, X2, R1, R2 and/or A, it may form a salt with a base. As the base used for this purpose, there may be mentioned inorganic bases such as sodium, potassium, lithium, calcium, magnesium, ammonia, etc. and organic bases such as pyridine, collidine, triethylamine, triethanolamine and so on. Where the compound [I] contains basic groups such as amino, substituted amino and/or other groups in its positions X1, X2, R1, R2 and/or A, it can form an acid addition salt. As examples of such acid addition salts, there may be mentioned hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, phosphate, acetate, benzoate, maleate, fumarate, succinate, tartarate, citrate, oxalate, glyoxalate, aspartate, methanesulfonate, methanedisulfonate, 1,2-ethanedisulfonate, benzenesulfonate and so on.
The compound [I] may form an inner salt, which also falls within the scope of the invention.
The compound [I] and its stereoisomer and tautomer (for example, where the compound [I] is a compound of the formula 
wherein the symbols have the meanings defined herein-before, its tautomer of the formula 
wherein the symbols have the meanings defined herein-before, also falls into the category of compound [I]) can be used, either independently or in the form of a mixture, as an insecticidal/miti(acari)cidal agent.
The compound [I] and its salt according to the invention are effective in the control of household pests and animal or plant parasitizing insects and mites, and exhibit strong pesticidal effects as a contact poison when applied directly to the host animals and plants. The most salient feature of the compound, however, is that it displays potent pesticidal effects even after it has been absorbed into plants via the root, leaf, stem or the like and come into contact with the pests as the pests suck or gnaw on the plants. This property is advantageous in the control of sucking/biting insets and ticks. Furthermore, the compound of the invention is of low toxicity to plants and fish, thus having safe and useful characteristics as an agricultural pesticide.
The compound [I] and its salts and compositions containing the same are particularly effective in the control of the following kinds of pests: pests of the order Hemiptera such as Euydema rugosum, Scotinophara lurida, Riptortus clavatus, Stephanitis nashi, Laodelphax striatellus, Nilaparvata lugens, Nephotettix cincticeps, Unaspis yanonensis, Aphis glycines, Lipaphis erysimi, Brevicoryne brassicae, Aphis gossypii, Sogattela furcifera, Nezara viridula, Trialeurodes vaporariorum, Myzus persicae, Pseudococcus comstocki, Aphis promi, Nezara spp., Cimex lectularius, Psylla spp., etc.; pests of the order Lepidoptera such as Spodoptera litura, Plutella xylostella, Pieris rapae crucivora, Chilo suppressalis, Plusia nigrisigna, Halicoverpa assulta, Leucania separata, Mamestra brassicae, Adoxophyes orana, Notarcha derogata, Cnaphalocrocis medinalis, Phthorimaea operculella, etc.; pests of the order Cleoptera such as Epilachna vigintioctopunctata, Aulacophora femoralis, Phyllotreta striotata, Oulema oryzae, Echinocnemus squameus, etc.; pests of the order Diptera such as Musca domestica, Culex pipiens pallens, Tabanus trigonus, Hylemyia antiqua, Hylemyia platura etc.; pests of the order Orthoptera such as Locusta migratoria, Gryllotalpa africana, etc., cockroaches such as Blattella germanica, Periplaneta fuliginosa, etc.; spider mites such as Tetranychus urticae, Panonychus citri, Tetranychus kanzawai, Tetranychus cinnabarinus, Panonychus ulmi, Aculops pelekassi, etc., and nematodes such as Aphelenchoides besseyi and so on.
For application of the compound [I] or salt of the invention as an insectide/miti(acari)cide, it can be formulated into any possible and desired application form for agrochemicals. Thus, by dissolving or dispersing one or more species of compound [I] and salt thereof in an appropriate liquid carrier or vehicle or admixing them with or causing them adsorbed on an appropriate solid carrier, an emulsifiable concentrate, oil preparation, wettable powders, dusts, granules, tablets, aerosol, ointment or the like can be manufactured. If necessary, such compositions may be further supplemented with emulsifiers, suspending agents, spreader-stickers, penetrating agents, wetting agents, thickeners, stabilizers and so on, and any of such preparations can be manufactured by the per se known procedures.
The concentration of the active ingredient (compound [I] or salt thereof) in such an insecticidal/miti(acari)cidal composition of the invention depends on the intended application. Generally speaking, the proper concentration is about 10 to 90 weight percent for emulsifiable concentrate and wettable powders, about 0.1 to 10 weight percent for oils and dusts and about 1 to 20 weight percent for granules, for instance. However, the concentration may be adjusted according to the intended application. In the case of an emulsifiable concentrate or a wettable powder, it is diluted with water or the like to a suitable concentration (for example, 100 to 100,000-fold dilution) before spraying.
The liquid carrier (solvent) includes, among others, water, alcohols (e.g. methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, ethylene glycol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, propylene glycol monomethyl ether, etc.), aliphatic hydrocarbons (e.g. kerosin, kerosene, fuel oil, machine oil, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, solvent naphtha, methylnaphthalene, etc.), halogenated hydrocarbons (e.g. methylene chloride, chloroform, carbon tetra-chloride, etc.), acid amides (e.g. dimethylformamide, dimethylacetamide, etc.), esters (e.g. ethyl acetate, butyl acetate, fatty acid glycerin esters, etc.), nitrites (e.g. acetonitrile, propionitrile, etc.) and so on. One of these solvents or a mixture of two or more of them can be used as the carrier.
The solid carrier (diluent-volume builder) includes, among others, vegetable powders (e.g. soybean flour, tobacco flour, wheat flour, sawdust, etc.), mineral powders (e.g. clays such as kaolin, bentonite, acid clay, etc., talcs such as talc, pyrophillite, etc. and silicates such as diatomaceous earth, mica powder, etc.), alumina, sulfur powder, activated carbon and so on. These powders can be used singly or as a mixture.
The ointment base that can be employed include, among others, any or a mixture of polyethylene glycol, pectin, higher fatty acid polyhydric alcohol esters such as monostearic acid glycerin ester etc., cellulose derivatives such as methylcellulose etc., sodium alginate, bentonite, higher alcohols, polyhydric alcohols such as glycerin, vaseline, white petrolatum, liquid paraffin, lard, vegetable oils, lanolin, anhydrous lanolin, hydrogenated oils, resins, etc., or mixtures thereof with the any of the following surfactants.
Surfactants which can be optionally used as said emulsifier, spreader/sticker, penetrating agent, dispersing agent, etc. include soaps and nonionic or anionic surfactants such as polyoxyethylene alkyl aryl ethers (e.g. Noigen, E. A. 142(copyright), manufactured by Daiichi Kogyo Seiyaku Co., Ltd., JAPAN; Nonal(copyright), Toho Chemical:, JAPAN), alkylsulfates (e.g. Emal 10(copyright), Emal 40(copyright), manufactured by Kao Corporation, JAPAN), alkylsulfonates (e.g. Neogen(copyright), Neogen T(copyright), manufactured by Daiichi Kogyo Seiyaku Co., Ltd.; Neopellex(copyright), manufactured by Kao Corporation), polyethylene glycol ethers (e.g. Nonipol 85(copyright), Nonipol 100(copyright), Nonipol 160(copyright), manufactured by Sanyo Chemical Industries, Ltd., JAPAN) and polyhydric alcohol esters (e.g. Tween 20(copyright), Tween 80(copyright), manufactured by Kao Corporation).
The compound of the invention can be used in combination with other insecticides (pyrethroid insecticides, organophosphorus insecticides, carbamate insecticides, natural insecticides, etc.), miticides (acaricides), nematocides, herbicides, plant hormones, plant growth regulators, fungicides (copper fungicides, organochlorine fungicides, organosulfur fungicides, phenolic fungicides, etc.), synergists, attractants, repellents, pigments, fertilizers and so on.
The resulting insecticide/miticide according to the invention is of low toxicity and safe and is an excellent agrochemical. The insecticidal/miticidal agent of the invention can be used in the same manner as the conventional insecticides and miticides and produces effects surpassing those of the latter. For example, the insecticidal/miticidal agent of this invention can be applied for control of pests by such procedures as nursery bed treatment, stem/foliage spray or dusting, direct application to pests, paddy water treatment, soil treatment and so on. The dosage can be selected from a broad range according to the timing, site and method of application. Generally speaking, the preferred dosage of the active ingredient (compound [I] or a salt thereof) per hectare is 0.3 g to 3,000 g and, for still better results, 50 g to 1,000 g. Where the insecticidal/miticidal agent of the invention is provided as a wettable powder, it can be used as diluted so that the final concentration of the active ingredient will be in the range of 0.1 to 1,000 ppm, preferably 10 to 500 ppm.